ACTIVE IMMUNIZATION BY A DENGUE VIRUS-INDUCED CYTOKINE

Dengue type 2 virus (DV)-induced cytotoxic factor (CF) is capable of r eproducing various pathological lesions in mice that are seen in human dengue. The present study was undertaken to investigate the protectiv e effect of active immunization of mice with CF. Mice were immunized w ith 5 mu g of CF and prevention of CF-induced increase in capillary pe rmeability and damage to the blood-brain barrier were studied at weekl y intervals, up to 48 weeks, by challenging with 3 mu g of CF. Maximum protection against increase in capillary permeability and damage to t he blood-brain barrier was observed in week 4 after immunization. A br eakthrough in the protection occurred with higher doses of CF in a dos e-dependent manner. Challenge with a lethal intracerebral (i.c.) dose of DV showed significantly prolonged mean survival time and delayed on set of symptoms of sickness in the immunized mice compared with the no rmal mice, but the titre of the virus in the brain was similar in the two groups. On i.p. challenge with the virus the protection against da mage to the blood-brain barrier was 86 +/- 7% at week 4 and 17 +/- 4% at week 26 after immunization. Sera obtained from the immunized mice s howed the presence of CF-specific antibodies by ELISA, Western blot, a nd by neutralization of the cytotoxic activity of CF in vitro. The pre sent study describes successful prevention of a cytokine-induced patho logy by specific active immunization.